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Using linear mixed-effects models, after adjusting for age, sex, BMI, tumor, cohort, date of stool sampling, patient ID (random effect) and pooling all time points of stool collection during immunotherapy ( n = 84 patients, 165 feces), we found that stool histidine (alongside other essential amino acids) inversely correlated with the occurrence of a severe irAEs (grade 3) (Extended Data Fig